A Multicenter, Open-label, Phase I Clinical Study to Evaluate the Safety, Pharmacokinetics, and Antitumor Efficacy of SIM0270 Alone or in Combination in Subjects with ER-positive, HER-2 Negative Locally Advanced or Metastatic Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 214
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose
研究概览
简要总结
This study is a multi-center, open-label, Phase 1 clinical study to evaluate the safety, pharmacokinetic (PK) and anti-tumor efficacy of SIM0270 and SIM0270 in combination with palbociclib or everolimus in subjects with estrogen receptor (ER) -positive, human epidermal growth factor receptor (HER-2) -negative locally advanced or metastatic breast cancer.
详细描述
The study is comprised of two parts: Phase Ia and Phase Ib. Phase Ia includes dose-escalating stage and dose expansion stageof SIM0270 monotherapy to determine the MTD/ RP2D and the preliminary safety and efficacy of SIM0270; Phase Ib includes 2 arms, armA: dose escalation and dose expansion of SIM0270 in combination with palbociclib; armB: dose escalation and dose expansion of SIM0270 in combination with palbociclib everolimus; phase Ib is designed to determine the MTD/RP2D and the preliminary safety and efficacy of SIM0270 in combination with palbociclib or everolimus.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •voluntary participation in clinical trials and signature of informed consent.
- •age ≥ 18 years, male or female.
- •Histologically or cytologically confirmed metastatic/locally advanced ER-positive, HER-2 negative breast cancer subjects.
- •previous treatment meets the criteria of the protocol defined.
- •ECOG score of 0 or 1 .
- •at least one measurable lesion that meets RECISTv1.1 criteria. Osteolytic lesions can be included in the Ia dose-escalating .
- •expected survival ≥ 12 weeks.
- •Adequate organ and bone marrow function.
- •Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to the first dose.
- •Postmenopausal women; Premenopausal or perimenopausal female subjects met protocol requirements.
排除标准
- •Documented medical history or ongoing gastrointestinal disease or other malabsorption that may affect the absorption of oral study drug.
- •Participated in other clinical trials of investigational drugs or investigational devices within 28 days before the first medication; or received chemotherapy, targeted therapy, immunotherapy and clinical trial medication and other anti-tumor treatment within 4 days or 5 half-lives of the first medication (whichever is shorter), or received radiotherapy, endocrine drugs or Chinese patent medicines with anti-tumor indications 2 weeks before the first medication;
- •The toxicity of previous anti-tumor treatment has not recovered to grade 0 or 1 (alopecia, chemotherapy-induced peripheral neurotoxicity ≤ grade 2 can be included).
- •Major surgical surgery (except biopsy) or incomplete healing of the surgical incision 4 times before the first study drug treatment;
- •Known other malignant tumors within 2 years before enrollment (except treated basal cell carcinoma, scaly cell carcinoma and/or radical carcinoma in situ);
- •Leptomeningeal metastasis confirmed by MRI or known cytology of CSF, or cranial Increased internal pressure or brain metastases with unstable central nervous symptoms (within 2 weeks prior to initial medication Treatment with any craniotropic, glucocorticokinin, or anticonvulsant);
- •Previous history of interstitial lung disease, drug-induced interstitial lung disease, symptomatic interstitial lung disease or any evidence of active pneumonia on chest CT scan 4 before the first study drug treatment;
- •known to interfere with the test requirements of mental illness or drug abuse disease.
- •History of human immunodeficiency virus HIV infection, or active bacterial or fungal infection requiring systemic treatment .
- •presence of active syphilis infection.
- •Subjects with known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection with abnormal liver function.
- •History of clinically significant cardiovascular disease.
- •History of serious allergic reactions to the study drugs or excipients used in the protocol.
- •Women who are pregnant or lactating.
- •Prior use of SERD oral medications.
- •Subjects who use drugs or herbal supplements known to be moderate/strong inhibitors of CYP3A 2 Weeks before the first dose.Or Subjects who use drugs or herbal supplements known to be moderate/strong inducers of CYP3A 4 weeks before the first dose.
- •Other conditions that the investigator considers unsuitable for this study.
研究组 & 干预措施
SIM0270
Phase Ia SIM0270 monotherapy dose escalation and expansion
干预措施: SIM0270 (Drug)
SIM0270+palbociclib
Phase Ib SIM0270 with palbociclib dose escalation and expansion
干预措施: SIM0270 (Drug)
SIM0270+palbociclib
Phase Ib SIM0270 with palbociclib dose escalation and expansion
干预措施: Palbociclib (Drug)
SIM0270+everolimus
Phase Ib SIM0270 with everolimus dose escalation and expansion
干预措施: SIM0270 (Drug)
SIM0270+everolimus
Phase Ib SIM0270 with everolimus dose escalation and expansion
干预措施: everolimus (Drug)
结局指标
主要结局
Maximum Tolerated Dose
时间窗: At the end of Cycle 1 (each cycle is 28 days)
Dose Escalation: Maximum Tolerated Dose (MTD) of SIM0270 When Administered as a Single Agent or in Combination with Palbociclib or Everolimus
recommended phase 2 Dose
时间窗: At the end of Cycle 1 (each cycle is 28 days)
Dose Escalation: recommended phase 2 Dose (RP2D) of SIM0270 When Administered as a Single Agent or in Combination with Palbociclib or Everolimus
Dose-Limiting Toxicities
时间窗: At the end of Cycle 1 (each cycle is 28 days)
Dose Escalation: Number of Participants with Dose-Limiting Toxicities When SIM0270 is Administered as a Single Agent or in Combination with Palbociclib or Everolimus
次要结局
- Adverse event(From Baseline until 30 days after the last dose of study treatment)
- Peak Plasma Concentration (Cmax) of SIM0270 as monotherapy or combination with palbociclib or everolimus(At the end of Cycle 4 (each cycle is 28 days))
- Time of Peak Plasma Concentration (Tmax) of SIM0270 as monotherapy or combination with palbociclib or everolimus(At the end of Cycle 4 (each cycle is 28 days))
- Area under the plasma concentration versus time curve (AUC) of SIM0270 as monotherapy or combination with palbociclib or everolimus(At the end of Cycle 4 (each cycle is 28 days))
- clinical benefit rate(through study completion, an average of 1 year)
- disease control rate(through study completion, an average of 1 year)
- duration of response(through study completion, an average of 1 year)
- progression free survival(From date of C1D1 until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months)
- time to progression(From date of C1D1 until the date of first documented progression, assessed up to100 months)
- time to response(through study completion, an average of 1 year)
- overall survival(From date of C1D1 until the date of death from any cause, assessed up to 100 months)
- overall response rate(through study completion, an average of 1 year)